In an effort to develop a laser system which would incorporate plaque recognition with tissue ablation, further developmental efforts utilizing a common fiber technology with fluorescence spectroscopy are being examined. We have helped to develop a prototype dual laser system incorporating a continuous helium cadmium laser (325nm) for fluorescence atheroma detection (probe mode) and a pulsed dye laser (480nm) for tissue ablation. Common optical fibers are used for light excitation of tissue, fluorescence detection, and tissue ablation. After fluorescent sensing, computer-based algorithms direct a fire-no fire signal to the dye laser at 7 repetitions per second for selective atheroma removal. Fluorescence detection of normal and variable composition atheroma were studied in necropsy specimens (n=261) from aorta, coronaries and leg arteries. Although distinctive fluorescence spectra patterns were associated with varying atheroma morphology, an algorithm of normalized spectra ratios differentiated normal sites from abnormal sites reliably (p less than .001). Probe and fire sequences were tested in normal sites and abnormal sites with 600u fibers demonstrating no laser firing on any normal sites, and correct identification with subsequent tissue ablation in 90% of abnormal sites. Importantly, there were no transmural perforations; firing stopped at the intima-media interface when fluorescence spectra returned to normal after atheroma was removed. We conclude from these preliminary studies that the concept of probe and fire dual laser angioplasty using fluorescence detection can effectively direct selective ablation in vitro and may provide the margin of safety necessary for efficacious in vivo laser angioplasty.